Lung disease models on a chip

Abstract

The presently disclosed subject matter provides a biomimetic lung disease model, and methods of its production and use. In one exemplary embodiment, the biomimetic lung disease model can include a first and second microchannel with a membrane coated with airway epithelial cells disposed between the microchannels and at least one device coupled to the biomimetic model that delivers an agent to at least one microchannel. In certain embodiments, the agent is cigarette smoke.

The invention claimed is: 
     
       1. A biomimetic lung model, comprising:
 a body having a first microchannel and a second microchannel disposed therein; 
 a membrane disposed between the first microchannel and the second microchannel, the membrane having a first side facing the first microchannel and a second side facing the second microchannel; 
 a layer of cells coating the first side of the membrane; and 
 tissue or cells embedded within a gel layer attached to the second side of the membrane, 
 wherein the layer of cells comprises airway epithelial cells. 
 
     
     
       2. The biomimetic lung model of  claim 1 , wherein the membrane comprises polyester, polydimethylsiloxane, polytetrafluoroethylene, polyurethane, paper, collagen, laminin, or a combination thereof. 
     
     
       3. The biomimetic lung model of  claim 1 , wherein at least one of the first microchannel and the second microchannel has a width from about 0.5 mm to about 2 mm and a length from about 1000 μm to about 10 mm. 
     
     
       4. The biomimetic lung model of  claim 3 , wherein the at least one of the first microchannel and the second microchannel has a width from about 1 mm to about 2 mm and a length of about 1000 μm. 
     
     
       5. The biomimetic lung model of  claim 1 , wherein the airway epithelial cells comprise Type I and Type II cells. 
     
     
       6. The biomimetic lung model of  claim 1 , wherein the layer of cells further comprises at least one type of macrophage cells selected from the group consisting of alveolar, interstitial, intravascular, airway macrophages, and an immortalized macrophage cell line. 
     
     
       7. The biomimetic lung model of  claim 1 , wherein the gel layer comprises one or more extracellular matrix proteins selected from the group consisting of collagen, fibronectin, laminin, and hyaluronic acid. 
     
     
       8. The biomimetic lung model of  claim 1 , wherein the embedded tissue or cells comprise one or more of basal stromal tissue and cells. 
     
     
       9. The biomimetic lung model of  claim 1 , wherein cells within the layer of cells are obtained from a healthy human lung or a chronically diseased human lung. 
     
     
       10. The biomimetic lung model of  claim 1 , wherein the embedded tissue or cells are in communication with the layer of cells on the first side of the membrane. 
     
     
       11. The biomimetic lung model of  claim 1 , wherein the airway epithelial cells comprise one or more of nasal epithelial cells, tracheal epithelial cells, and small airway epithelial cells. 
     
     
       12. A method for fabricating a biomimetic lung disease model, comprising:
 (a) fabricating a body, the body having a first microchannel and a second microchannel disposed therein; 
 (b) inserting a membrane between the first microchannel and the second microchannel, the membrane having a first side facing the first microchannel and a second side facing the second microchannel; 
 (c) adhering a layer of cells on a surface of at least the first side of the membrane; and 
 (d) casting a tissue-or cell-laden gel on a surface of the second side of the membrane, the gel being configured to solidify by incubation at body temperature, 
 wherein the layer of cells comprises airway epithelial cells. 
 
     
     
       13. The method of  claim 12 , wherein adhering the layer of cells comprises seeding a high-density cell suspension on the surface of the first side of the membrane and incubating the cell suspension for about 2 to about 4 hours. 
     
     
       14. The method of  claim 12 , wherein the layer of cells further comprises macrophage cells. 
     
     
       15. The method of  claim 14 , wherein the macrophage cells comprise at least one selected from the group consisting of alveolar, interstitial, intravascular, airway macrophages, and an immortalized macrophage cell line. 
     
     
       16. The method of  claim 12 , wherein the membrane comprises polyester, polydimethylsiloxane, polytetrafluoroethylene, polyurethane, paper, collagen, laminin, or a combination thereof. 
     
     
       17. The method of  claim 12 , wherein the airway epithelial cells comprise Type I and Type II cells. 
     
     
       18. The method of  claim 12 , wherein the tissue-or cell-laden gel comprises one or more of basal stromal tissue and cells. 
     
     
       19. The method of  claim 12 , wherein the layer of cells comprises cells obtained from a healthy human lung or from a chronically diseased human lung.